A transcriptional signature of PDGF-DD activated natural killer cells predicts more favorable prognosis in low-grade glioma
- Author(s)
- Sun, Y; Sedgwick, AJ; Palarasah, Y; Mangiola, S; Barrow, AD;
- Journal Title
- Frontiers in Immunology
- Abstract
- The binding of platelet-derived growth factor D (PDGF-DD) to the NKp44 receptor activates a distinct transcriptional program in primary IL-2 expanded human natural killer (NK) cells. We were interested in knowing if the PDGF-DD-NKp44 pathway of NK cell activation might play a clinically relevant role in anti-tumor immunity. In order to address this question, we determined transcriptional signatures unique to resting, IL-2 expanded, and PDGF-DD activated, NK cells, in addition to different T cell subsets, and established the abundance of these immune cell phenotypes in The Cancer Genome Atlas (TCGA) low-grade glioma (LGG) dataset using CIBERSORT. Our results show that LGG patient tumors enriched for either the PDGF-DD activated NK cell or memory CD8(+) T cell phenotypes are associated with a more favorable prognosis. Combined cell phenotype analyses revealed that patients with LGG tumors enriched for the PDGF-DD activated NK cell phenotype and the CD4(+) T helper cell phenotype had a more favorable prognosis. High expression of transcripts encoding members of the killer cell lectin-like receptor (KLR) family, such as KLRK1 and KLRC2, KLRC3 and KLRC4 in LGG tumors were associated with more favorable prognosis, suggesting that these NK cell family receptors may play a prominent role in LGG anti-tumor immunity. Finally, many of the TCGA findings were reciprocated in LGG patients from the Chinese Glioma Genome Atlas (CGGA) dataset. Our results provide transcriptomic evidence that PDGF-DD activated NK cells and KLR family receptors may play an important clinical role in immune surveillance of LGG.
- Publisher
- Frontiers Media
- Keywords
- *NK cell; *NK cell receptor; *The Cancer Genome Atlas; *anti-tumor immunity; *low grade glioma
- Research Division(s)
- Bioinformatics
- PubMed ID
- 34539622
- Publisher's Version
- https://doi.org/10.3389/fimmu.2021.668391
- Open Access at Publisher's Site
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Creation Date: 2021-10-12 07:30:15
Last Modified: 2021-10-19 11:21:45